Molecular mechanisms of ROS-modulated cancer chemoresistance and therapeutic strategies

Drug resistance is the main obstacle to achieving a cure in many cancer patients. Reactive oxygen species (ROS) are master regulators of cancer development that act through complex mechanisms. Remarkably, ROS levels and antioxidant content are typically higher in drug-resistant cancer cells than in non-resistant and normal cells, and have been shown to play a central role in modulating drug resistance. Therefore, determining the underlying functions of ROS in the modulation of drug resistance will contribute to develop therapies that sensitize cancer resistant cells by leveraging ROS modulation. In this review, we summarize the notable literature on the sources and regulation of ROS production and highlight the complex roles of ROS in cancer chemoresistance, encompassing transcription factor-mediated chemoresistance, maintenance of cancer stem cells, and their impact on the tumor microenvironment. We also discuss the potential of ROS-targeted therapies in overcoming tumor therapeutic resistance.

Automated summary

Drug resistance is a major obstacle in curing cancer patients. Reactive oxygen species (ROS) play a crucial role in modulating drug resistance in cancer cells, with higher levels seen in drug-resistant cells compared to non-resistant cells. Understanding the functions of ROS in drug resistance can help develop therapies to sensitize cancer cells. This review summarizes literature on ROS production, regulation, and their complex roles in cancer chemoresistance, including transcription factor-mediated resistance and impact on the tumor microenvironment. The potential of ROS-targeted therapies in overcoming therapeutic resistance is also discussed.